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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Arsenic Trioxide Induces Apoptosis in Chronic Myelogenous Leukemia K562 Cells:Possible Involvement of p38 MAP Kinase

  • Shim, Moon-Jeong (Department of Biomedical Laboratory Science, College of Health Science, Yonsei University) ;
  • Kim, Hyun-Jeong (Department of Biomedical Laboratory Science, College of Health Science, Yonsei University) ;
  • Yang, Seung-Ju (Department of Biomedical Laboratory Science, College of Health Science, Yonsei University) ;
  • Lee, In-Soo (Department of Biomedical Laboratory Science, College of Health Science, Yonsei University) ;
  • Choi, Hyun-Il (Department of Biomedical Laboratory Science, College of Health Science, Yonsei University) ;
  • Kim, Tae-Ue (Department of Biomedical Laboratory Science, College of Health Science, Yonsei University)
  • Published : 2002.07.31
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Abstract

Arsenic trioxide ($As_O_3$) was recently demonstrated to be an effective inducer of apoptosis in patients with relapsed acute promyelocytic leukemia (APL) as well as patients with APL in whom all-trans-retinoic acid and conventional chemotherapy failed. Chronic myelogenous leukemia cells are highly resistant to chemotherapeutic drugs. To determine if $As_O_3$ might be useful for the treatment of chronic myelogenous leukemia, we examined the ability of $As_O_3$ to induce apoptosis in K562 cells. In vitro cytotoxicity of $As_O_3$ was evaluated in K562 cells by a MTT assay: the $IC_50$ value for $As_O_3$ was determined to be $10\;{\mu}m$. When analyzed by agarose gel electorphoresis, the DNA fragments became evident after incubation of the cells with $20\;{\mu}m$ $As_O_3$ for 24 h. We also found morphological changes and chromatin condensation of the cells undergoing apoptosis. Activation of caspase-3 was observed 6 h after treatment with $20\;{\mu}m$ $As_O_3$ by a Western blot analysis. Next, we examined the MAP kinase-signaling pathway of $As_O_3$-induced apoptosis in K562 cells. $As_O_3$ at $10\;{\mu}m$ strongly induced the activation of p38, inhibited $As_O_3$ induced apoptotic cell death. These results suggest that $As_O_3$ is able to induce the apoptotic activity in K562 cells, and its apoptotic mechanism may be associated with the activation of p38.

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References

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